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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cells.
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The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cells.

机译：美金刚对人神经母细胞瘤SH-SY5Y细胞中星形孢菌素，沙丁胺醇和阿霉素诱导的细胞凋亡的减弱作用。

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摘要

Memantine, a clinically used N-methyl-D-aspartate (NMDA)-receptor antagonist, has been shown to prevent apoptotic neuronal damage connected with the over-activity of NMDA receptors. In the present study, we examined the effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in the SH-SY5Y cell line which does not possess functional NMDA receptors. Electrophysiological recordings and toxicity studies showed no response to NMDA-evoked currents in this cell line, irrespective of the stage of its neuronal differentiation. Memantine (0.1-2 microM) attenuated staurosporine-induced apoptosis as evidenced by reversal of the changes in mitochondrial membrane potential (DeltaPsi(m)) and decreased caspase-3 activity, lactate dehydrogenase (LDH) release and DNA fragmentation. Wortmannin (10 nM) and LY 294002 (10 microM) (inhibitors of phosphatidylinositol-3-kinase, PI3-K) reversed the inhibitory effect of memantine on the staurosporine-induced LDH release, suggesting that the PI3-K/Akt prosurvival pathway is a possible target for antiapoptotic action of memantine. Memantine at low micromolar concentrations also attenuated salsolinol- and doxorubicin-induced LDH release and DNA fragmentation, but only in the case of salsolinol was this effect accompanied by a decrease in caspase-3 activity. The present data indicate that memantine attenuates the toxic effects of various proapoptotic agents and the cytoprotective effect of memantine does not seem to be connected with its action on NMDA receptor but rather with its influence on intracellular pathways engaged in cellular survival/apoptotic processes.
机译：美金刚胺是临床上使用的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已被证明可以预防与NMDA受体过度活跃有关的凋亡性神经元损伤。在本研究中，我们研究了美金刚对不具有功能性NMDA受体的SH-SY5Y细胞系中金红霉素，沙丁胺醇和阿霉素诱导的细胞凋亡的影响。电生理记录和毒性研究表明，在该细胞系中，无论其神经元分化的阶段如何，对NMDA诱发的电流均无反应。美金刚胺（0.1-2 microM）减弱了线粒体膜电位（DeltaPsi（m））的变化和降低的caspase-3活性，乳酸脱氢酶（LDH）释放和DNA片段化，从而证明了星形孢菌素诱导的细胞凋亡。 Wortmannin（10 nM）和LY 294002（10 microM）（磷脂酰肌醇3-激酶抑制剂PI3-K）逆转了美金刚对星形孢菌素诱导的LDH释放的抑制作用，表明PI3-K / Akt的生存途径是美金刚抗凋亡作用的可能目标。低微摩尔浓度的美金刚胺也减弱了萨索林醇和阿霉素诱导的LDH释放和DNA片段化，但是仅在萨索林醇的情况下，这种作用伴随caspase-3活性的降低。本数据表明美金刚减少了各种促凋亡剂的毒性作用，美金刚的细胞保护作用似乎与其对NMDA受体的作用无关，而与其对参与细胞存活/凋亡过程的细胞内途径的影响有关。

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